Dataset Information

Proteomic analysis of endometrioid and high-grade serous ovarian tumour samples

ABSTRACT: Precision medicine approaches in ovarian cancer require the accurate diagnosis of histotypes. In particular, there is a critical need to distinguish endometroid (EC) from high grade serous (HGSC) carcinomas, which differ greatly in outcomes, genetic predisposition and optimal treatment approaches. Herein, we performed label-free quantitative proteomics on freshly frozen tumour tissues to discover biomarkers that may distinguish EC from HGSC, and then used IHC to validate these using a contemporarily classified cohort of EC and HGSC samples.

INSTRUMENT(S): Exactive Plus, LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Ovary, Ovary Cancer Cell

DISEASE(S): Ovarian Cancer,Ovarian Serous Carcinoma,Endometrioid Ovary Carcinoma

SUBMITTER: Dylan Dieters-Castator

LAB HEAD: Gilles A. Lajoie

PROVIDER: PXD012998 | Pride | 2019-03-13

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	HUMAN_25052017_reviewed_uniprot-all.fasta	Fasta
	MaxQuant_proteinGroups_OrbitrapEliteData.txt	Txt
	MaxQuant_proteinGroups_QExactivePlusData.txt	Txt
	Sample_information.xlsx	Xlsx
	dc_07102018_OV_tumours_T1.raw	Raw

Items per page:

1 - 5 of 70

Publications

Proteomics-Derived Biomarker Panel Improves Diagnostic Precision to Classify Endometrioid and High-grade Serous Ovarian Carcinoma.

Dieters-Castator Dylan Z DZ Rambau Peter F PF Kelemen Linda E LE Siegers Gabrielle M GM Lajoie Gilles A GA Postovit Lynne-Marie LM Köbel Martin M

Clinical cancer research : an official journal of the American Association for Cancer Research 20190412 14

<h4>Purpose</h4>Ovarian carcinomas are a group of distinct diseases classified by histotypes. As histotype-specific treatment evolves, accurate classification will become critical for optimal precision medicine approaches.<h4>Experimental design</h4>To uncover differences between the two most common histotypes, high-grade serous (HGSC) and endometrioid carcinoma, we performed label-free quantitative proteomics on freshly frozen tumor tissues (HGSC, <i>n</i> = 10; endometrioid carcinoma, <i>n</i> ...[more]

PMID: 30979743

Similar Datasets

Project description:Recent evidence suggests that ovarian high-grade serous carcinoma (HGSC) originates from the epithelium of the fallopian tube. However, most mouse models are based on the previous prevailing view that ovarian cancer develops from the transformation of the ovarian surface epithelium. Here, we report the extensive histological and molecular characterization of the mogp-TAg transgenic mouse, which expresses the SV40 large T-antigen (TAg) under the control of the mouse müllerian-specific Ovgp-1 promoter. Histologic analysis of the fallopian tubes of mogp-TAg mice identified a variety of neoplastic lesions analogous to those described as precursors to ovarian HGSC. We identified areas of normal appearing p53-positive epithelium that are similar to “p53 signatures” in the human fallopian tube. More advanced proliferative lesions with nuclear atypia and epithelial stratification were also identified that were morphologically and immunohistochemically reminiscent of human serous tubal intraepithelial carcinoma (STIC), a potential precursor of ovarian HGSC. Beside these noninvasive precursor lesions, we also identified invasive adenocarcinoma in the ovary of 56% of the mice. Microarray analysis revealed several genes differentially expressed between the fallopian tube of mogp-TAg and WT C57BL/6. One of these genes, Top2a, which encodes topoisomerase II-alpha, was shown by immunohistochemistry to be concurrently expressed with elevated p53 and specifically elevated in mouse STICs, but not in surrounding tissues. TOP2A protein was also found elevated in human STICs, low-grade, and high-grade serous carcinoma. The mouse model reported here displays a progression from normal tubal epithelium to invasive HGSC in the ovary, and therefore closely simulates the current emerging model of human ovarian HGSC pathogenesis. This mouse therefore has the potential to be a very useful new model for elucidating the mechanisms of serous ovarian tumorigenesis, as well as for developing novel approaches for the prevention, diagnosis, and therapy of this disease. Keywords: transgenic mouse model, ovarian cancer, fallopian tube, intraepithelial carcinoma 6 mouse fallopian tubes (FT) were analyzed with experimental repeats; 3 wildtype C57BL6 mice (FT) and 3 transgenic mogp-TAg (FT), with one set of each at 7, 8 and 9 weeks of age.